We will seek to determine the precise site of mitochondrial inhibition by CuKTS and ZnKTSM2 and the chemical nature of this inhibition. Then we will proceed to examine tumor cell mitochondria for similar effects. Our structure-function correlations will be extended to the mitochondrial systems. Effort will be directed toward evaluating the relative roles of inhibition of mitochondrial respiration and DNA synthesis in the mechanism of tumor cell cytotoxicity due to CuKTS and ZnKTSM2. Finally, we will use 2-formlypyridine thiosemicarbazone for comparisons in these studies, for its iron complex seems specific for the inhibition of DNA synthesis but its copper chelate can prevent mitochondria respiration.